Stable and accurate molecular dynamics (MD) of B-DNA duplexes can be obtained in inexpensive computational conditions where only the minor groove is filled with water while the bulk solvent is represented implicitly. Independent observations suggest that this ``minimal B-DNA'' resembles its natural thermodynamic state at low water pressure. Based upon this finding we tried to get a better insight in the possible physical origin of intrinsic bends induced in B-DNA by repeated adenine tracts. This long known but still unexplained phenomenon plays a key role in DNA studies because it is unique in the amount and the variety of the available experimental information and, therefore, is likely to serve as a gate to the unknown general mechanisms of recognition and regulation of genome sequences.
We have found A-tract motives that induce stable and properly directed static curvature in the minimal B-DNA. The bending emerges spontaneously in conditions excluding any initial bias except the base pair sequence. Important qualitative details suggest that the final bent state is a strong attractor of trajectories form a broad domain of the conformational space. Unexpectedly, the local sequence dependent conformational patterns in the ensemble of curved conformations appear strongly heterogeneous, in contradiction to all existing theoretical models of bending. Analysis of these observations leads to a new, significantly different hypothesis of the possible mechanism of intrinsic bends in the double helical DNA and suggests existence of microscopically heterogeneous macroforms, rather than definite specific DNA structures responsible for the biological activity.
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